ATRELAX (Atracurium Besylate)

        ATRELAX (Atracurium Besylate)

ATRELAX (Atracurium Besylate)

ATRELAX (Atracurium Besylate)

DESCRIPTION

Atracurium Besylate is an intermediate-duration, non-depolarizing, skeletal muscle relaxant for intravenous administration 

Atracurium Besylate is deigned as 2-(2-Carboxyethyl)-1,2,3,4-tetrahydro-6,7dimethoxy-2-methyl-1 veratrylisoquilolinium 

benzenesulfonate, pentamethylene ester, it has a molecular weight of 1243.49, and its molecular formula is C H N O S The 65 82 2 18 2. structural formula is:

Atracurium Besylate is a complex molecule containing four sites at which different stereochemical configurations can occur. The symmetry of the molecule, however, results in only ten. indeed of sixteen, possible different isomers. The manufacture of Atracurium 

Besylate results in three isomers being produced in unequal amounts but with a consistent ratio. Those motoculea in which the methyl group attached to the quaternary nitrogen projects on the opposite aide to the adjacent substituted-bnzyl moiety predominate by 

approximately 3 1. Atracurium Besylate Injection is a sterile, non-pyrogenic aqueous solution. Each mL contains Atracurium Besylate 10 mg and 

benzenesulfonic acid for pH adjustment pH 3 25 to 3.65 Atracurium Besylate Injection slowly loses potency with time at a rate of 

Oapproximately 6% per year under refrigeration (5 C). ATRELAX infection should be refrigerated at 2 to 8 C (36 to 46 F) to O Opreserve potency. Rale of loss in potency increases to approximately 5% per month at 25 C (77 F). Upon removal from refrigeration O O to room temperature storage conditions (25 C / 77 F), use ATRELAX Injection within fourteen days even if re-refrigerated

CLINICAL PHARMACOLOGY

Atracurium Besylate is a non-depolarizing skeletal muscle relevant. Non-depolarizing agents antagonize the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plate. This antagonism ia inhibited. and 

neuromuscular block reversed, by acetylchotinesterase inhibitors such as neostigmine, edrophonium, and pyridostigrine.

ATRELAX can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation.

The duration of neuromuscular blockade produced by ATRELAX is approximately one-third to one-half the duration of block by d-tubocufsnoe, metocurine. and pancuronium at initially equipotent doses. As with other non-depolarizing neuromuscular blockers. the 

time to onset of paralysis decreases and the duration of maximum effect increases with increasing ATRELAX doses.

The ED96 (dose required to produce 95% suppresssion of the muscle twitch response with balanced anaesthesia) has averaged 0.23 mg/kg (0.11 - 0.26 mg/kg in various studies). An initial ATRELAX dose of 0.4-0.5 mg/kg generally produces maximum 

neuromuscular block within 3 to 5 minutes of injection, with good or excellent intubation conditions within 2 to 2.5 minutes in most patients. Recovery from neuromuscular block (under balanced anaesthesia) can be expected to begin approximately 20 to 35 minutes after injection. Under balanced anaesthesia, recovery to 25% of control is achieved approximately 35 to 45 minutes attar 

inject ion, and recovery ia usually 95% complete approximately 60 to 70 minutes after injection. The neuromuscular blocking action of ATRELAX is enhanced in the presence of potent inhalation anaesthetic. Isoflurane, enflurane, desflurane, and sevoflurane increase the potency of ATRELAX and prolong neuromuscular block by approximately 35%; however, halothane's potentiating effect 

(approximately 20%) is marginal (see DOSAGE AND ADMINISTRATION)

Repeated administration of maintenance doses of ATRELAX has no cumulative effect on the duration of neuromuscular block ft 

recovery is slowed to begin prior to repeat dosing. Moreover, the time needed to recover from repeal doses does not change with additional doses. Repeal doses can therefore be administered at relatively regular intervals with predictable results. After an initial dose of 0.4 to 0.5 mg/kg under balanced anaesthesia, the first maintenance dose (suggested maintenance dose is 0.08 to 0.10 mg/kg) it generally required within 20 to 45 minutes, and subsequent maintenance doses are usually required at approximately 15 to 

25 minute intervals.Once recovery from ATRELAX neuromuscular blocking effects begins, it proceeds more rapidly than recovery from d-tubocuranne, 

metocurine, and pancuronium. Regardless of ATRELAX does, the time from start of recovery (from complete block) to completes (95%) recovery is approximately thirty minutes under balanced anaesthesia, and approximately forty minutes under halothane, 

enflurane, sevoflurane or desflurane and isoflurane. Repeated doses have no cumulative effect on recovery rate.

Reversal of neuromuscular block produced by ATRELAX can be achieved with an anticholinesterase agent such as neostigmine, 

edrophonium, or pyridostigmine, in conjunction with an anticholinergic agent such as atropine or glycopyrrolate. Under balanced anaesthesia, reversal can usually be attempted approximately 20 to 35 minutes after an initial Atracurium dote of 0.4 to 0.5 mg/kg, or approximately 10 to 30 minutes after a 0.08 to 0.10 mg/kg maintenance dose, when recovery of muscle twitch has started. 

Complete reversal is usually attained within 8 to 10 minutes of the administration of reversing agents Rare instances of breathing difficulties, possibly related to incomplete reversal, have been reported following attempted pharmacologic antagonism of Atracurium-induced neuromuscular block. As with other agents in this class, the tendency tor residual neuromuscular block to increased il reversal is attempted at deep levels of block or if inadequate doses of reversal agents are employed.